During the past year, there have been two areas of research ongoing in the Molecular Immunology Section: 1) identification of structure/function relationships of human CD8+ T cell antigen-specific receptors (TCR) and 2) determination of differential gene expression in CNS lesions of MS patients. Structural analysis of TCR recognition has been examined using T cell assays, kinetic and thermodynamic binding assays, and X-ray crystallography. Three singly substituted peptide variants of the HTLV-I Tax peptide that represent a weak agonist and two weak antagonists were shown to have different affinities for the Tax-specific A6 TCR. The three-dimensional structures of these three peptide/MHC complexes bound by the A6 TCR revealed remarkably similar structures compared to the wild-type agonist Tax peptide, with minor adjustments at the interface to accomodate the peptide substitutions (P6A, V7R, and Y8A). The absence of correlation between structural changes and the type of T cell signals induced provides direct evidence that different signals are not generated by different ligand-induced conformational changes in the abTCR. Analysis of differential gene expression in CNS lesions of MS patients by cDNA microarray technology has been performed by monitoring the expression pattern of over 5,000 genes. Sixty-two genes expressed in lesions compared to normal white matter of a single patient were identified. These genes included the Duffy chemokine receptor, IRF-2, and the TNF-alpha receptor-2, indicating the presence of components of inflammatory processes not previously seen in MS lesions. Thus, cDNA microarray technology represents a powerful new tool for the identification of genes not previously associated with the MS disease process. - multiple sclerosis, T cell receptors, microarray cDNA analysis